Rationale and Design of a Phase II Trial of Combined Serplulimab and Chemotherapy in Patients with Histologically Transformed Small Cell Lung Cancer: a Prospective, Single-arm and Multicentre Study.

AIMS: Transformed small cell lung cancer (T-SCLC) is a highly aggressive clinical disease with a notably poor prognosis. It most often arises from epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) following treatment. To date, no standard treatment has been established for T-SCLC. Platinum-etoposide was the most commonly used regimen, but progression-free survival remains unsatisfactory. Therefore, there is an urgent unmet need to develop novel and effective strategies for this population. Our study, a multicentre, open-label, single-arm phase II clinical trial (NCT05957510), aims to evaluate the efficacy and safety of serplulimab plus chemotherapy in untreated T-SCLC patients after histological transformation. MATERIALS AND METHODS: In total, 36 eligible participants experiencing SCLC transformation from EGFR-mutant NSCLC will be enrolled to receive combination therapy of serplulimab, etoposide and carboplatin for four to six cycles, followed by maintenance therapy with serplulimab for up to 2 years. The primary endpoint is progression-free survival; secondary endpoints include objective response rate, overall survival and safety. RESULTS: Enrolment started in July 2023 and is ongoing, with an estimated completion date of December 2025. CONCLUSIONS: This study aims to provide valuable insights into the efficacy and safety of combining serplulimab with chemotherapy for treating patients with T-SCLC originating from EGFR-mutant NSCLC.

[Clinical effects of scalp flaps pedicled with superficial temporal artery parietal branch in repairing facial destructive burn wounds].

Objective: To explore the clinical effects of scalp flaps pedicled with superficial temporal artery parietal branch in repairing facial destructive burn wounds. Methods: A retrospective observational study was conducted. From January 2016 to December 2021, 15 patients with facial destructive burns who met the inclusion criteria were admitted to Zhengzhou First People's Hospital, including 11 males and 4 females, aged 22 to 79 years. Two patients were complicated with unilateral eyeball destructive burns, two patients were complicated with unilateral auricle defects, eight patients were complicated with lip and cheek defects, and three patients were complicated with lip, cheek, and unilateral nasal alar defects. The burn wound areas ranged from 9 cm×6 cm to 13 cm×10 cm. The scalp flaps pedicled with superficial temporal artery parietal branch, with the area of 10 cm×7 cm to 15 cm×11 cm, were designed, excised, and transferred for repairing burn wounds. The secondary wounds at the donor sites were repaired with medium-thickness scalp grafts. According to patient's needs, the hairs grew at the facial transplanted flap were removed by laser at 2 weeks after the flap was completely viable, or the expanded scalp flap was used to treat the secondary alopecia in the flap donor area of the head at 3 months after the primary wound repair. The survival of the flap/skin graft and the wound healing of the donor and recipient areas after the primary wound repair were recorded. During the follow-up, the appearance of the flap, the scar hyperplasia at the suture site, the repair effect of facial functional parts, the treatment effects of laser hair removal and secondary alopecia treatment at the flap donor site were observed; the patient's satisfaction with the overall repair effect was inquired. Results: After the primary wound repair, all the flaps transplanted to the burn wounds and the skin grafts transplanted to the secondary wounds of the flap donor sites survived well, and the wounds at the donor and recipient sites of flap healed well. The color, texture, and thickness of flap were basically the same as those of normal facial skin, and the scar at the suture site was slight during 3 to 18 months of follow-up period after the primary wound repair. In 11 patients complicated with lip defects, the oral integrity, and the opening and closing functions of mouth were restored with the mouth opening being 2.0-2.5 cm and no microstomia; all the patients could carry out basic language communication, 8 of them could take regular food, and 3 of them could take soft food. The wounds in two patients with unilateral eyeball destructive burns were repaired. In 2 patients complicated with auricle defects, the wounds were repaired, and the external auditory canals were normal. In 3 patients complicated with unilateral nasal alar defects, their noses had poor appearance with reduced nostrils. No hair growth was observed in the facial flap sites after treatment of laser hair removal in 8 patients. Five patients were successfully treated with expanded scalp flaps for secondary alopecia in the flap donor area of the head. The patients were all satisfied with the overall repair effect. Conclusions: The scalp flap pedicled with superficial temporal artery parietal branch has abundant blood supply and is suitable for repairing the wounds in facial destructive burns. It is easy to transfer and can better restore the appearance and function of the recipient area with minimal damage to the flap donor area, which is worthy of clinical promotion.

[Effects of free gracilis muscle flap combined with sural nerve transfer for reconstruction of digital flexion and sensory function of hand in patient with wrist electric burn].

Objective: To explore the effects of free gracilis muscle flap combined with sural nerve transfer for reconstruction of digital flexion and sensory function of hand in patient with severe wrist electric burn. Methods: A retrospective observational study was conducted. From January 2017 to December 2020, 4 patients with wrist high-voltage electric burn admitted to the Department of Burns of the First People's Hospital of Zhengzhou and 4 patients with wrist high-voltage electric burn admitted to the Department of Hand Surgery of Beijing Jishuitan Hospital met the inclusion criteria, including 6 males and 2 females, aged 12 to 52 years. They were all classified as type Ⅱ wrist high-voltage electric burns with median nerve defect. In the first stage, the wounds were repaired with free anterolateral thigh femoral myocutaneous flap. In the second stage, the free gracilis muscle flap combined with sural nerve transplantation was used to reconstruct the digital flexion and sensory function of the affected hand in 3 to 6 months after wound healing. The cut lengths of muscle flap and nerve were 32 to 38 and 28 to 36 cm, respectively. The muscle flap donor area and nerve donor area were both closed and sutured. The survival condition of gracilis muscle flap and sural nerve, the wound healing time of recipient area on forearm, the healing time of suture in muscle flap donor area and nerve donor area were observed and recorded after operation, and the recovery of donor and recipient areas was followed up. In 2 years after operation, the muscle strength of thumb and digital flexion and finger sensory function after the hand function reconstruction were evaluated with the evaluation criteria of the hand tendon and nerve repair in the trial standard for the evaluation of functions of upper limbs of Hand Surgery Society of Chinese Medical Association. Results: All the gracilis muscle flap and sural nerve survived successfully after operation. The wound healing time of recipient area on forearm was 10 to 14 days after operation, and the healing time of suture in muscle flap donor area and nerve donor area was 12 to 15 days after operation. The donor and recipient areas recovered well. In the follow-up of 2 years after operation, the muscle strength of thumb and digital flexion was evaluated as follows: 4 cases of grade 5, 3 cases of grade 4, and 1 case of grade 2; the finger sensory function was evaluated as follows: 4 cases of grade S3+, 2 cases of grade S3, and 2 cases of grade S2. Conclusions: For patients with hand dysfunction caused by severe wrist electric burn, free gracilis muscle flap combined with sural nerve transplantation can be used to reconstruct the digital flexion and sensory function of the affected hand. It is a good repair method, which does not cause great damage to thigh muscle flap donor area or calf nerve donor area.

[Curative effects of foot microflap free transplantation in the repair of full-thickness electric burn wounds deep to tendon or even bone in fingers].

Objective: To explore the curative effects of foot microflap free transplantation in the repair of full-thickness electric burn wounds deep to tendon or even bone in fingers. Methods: A retrospective observational study was conducted. From July 2017 to February 2022, 20 patients with full-thickness electric burn wounds deep to tendon or even bone in fingers who met the inclusion criteria were admitted to Zhengzhou First People's Hospital, including 19 males and 1 female, aged 18 to 64 years. Among the 20 wounds, 15 wounds were located on the palm side, including 8 on the thumb, 5 on the index finger, and 2 on the middle finger; 5 wounds were located on the back, including 1 on the index finger and 4 on the middle finger. After debridement, the wound area ranged from 4.5 cm×2.0 cm to 7.0 cm×3.0 cm. According to the principle of tissue structure similarity, 10 wounds were repaired with plantar medial flaps, 5 wounds were repaired with hallux peroneal flaps, and 5 wounds were repaired with dorsalis pedis artery flaps, with flap area of 5.0 cm×2.5 cm-8.0 cm×3.5 cm. The flaps were transplanted freely and arteries and veins and/or nerves were anastomosed at the same time. The wound in the donor site was repaired with thigh medium-thick skin graft. The survival of flaps and skin grafts were observed after surgery. The appearance of flap, temperature and color of the distal end in the affected finger were observed during follow-up. At the last follow-up, the joint function and flap sensory recovery of the affected finger were evaluated with the trial standard for the evaluation of the functions of the upper limbs of the Hand Surgery Society of the Chinese Medical Association; the two-point discrimination distance of skin in the area of flaps with nerve anastomosis was measured; the satisfaction of patients with the curative effect was investigated by using the curative effect satisfaction rating scale, and the very satisfied rate was calculated; the repair effect of flap was evaluated by the comprehensive evaluation scale, and the excellent and good rate was calculated. Results: All the flaps and skin grafts survived after surgery. During the follow-up of 10-18 months after surgery, the appearance of flap was natural and not bloated; the temperature and color of the distal end in the affected finger were basically the same as that of normal finger skin. At the last follow-up, the function recovery of the affected finger joints was as follows: 11 affected fingers were within the normal range of motion, 6 affected fingers had their total active range of motion recovered to 85% of the healthy side, and 3 affected fingers had their total active range of motion recovered to 75% of the healthy side; the flap sensory recovery was as follows: the sense of 15 flaps with nerve anastomosis all recovered to grade S3+, and the two-point discrimination distance of skin in the flap area was 7.0-9.0 mm; the sense of 1 flap without nerve anastomosis recovered to grade S2 and the sense of 4 flaps recovered to grade S1. The satisfaction with curative effect of 20 patients was very satisfied in 16 cases and moderately satisfied in 4 cases, with the very satisfied rate of 80%; the repair result of 20 flaps was excellent in 16 cases, good in 2 cases, and fair in 2 cases, with excellent and good rate of 90%. Conclusions: Due to the similar tissue structure of donor site and recipient site, foot microflap free transplantation in the repair of full-thickness electric burn wounds deep to tendon or even bone in fingers can achieve good appearance and function, with better functional and sensory recovery of the affected finger in the case of nerve anastomosis. Patients have high degree of satisfaction with the curative effects, which is worthy of promotion.

[Curative effects of ultrathin anterolateral femoral flap in one-stage split-finger repair of palmar combined with multiple finger wounds].

Objective: To explore the curative effects of ultrathin anterolateral femoral flap in one-stage split-finger repair of palmar combined with multiple finger wounds. Methods: A retrospective observational study was conducted. From October 2016 to June 2018, 20 patients with wounds on palms and multiple fingers who met the inclusion criteria were admitted to Zhengzhou First People's Hospital, including 15 males and 5 females, aged 18 to 77 years. After debridement, the wound area was 8 cm×4 cm-17 cm×12 cm. The wound was repaired by ultrathin anterolateral femoral flap with area of 9 cm×5 cm to 19 cm×13 cm. According to the wound condition of finger, the finger division was performed in one stage, and the length-to-width ratio of the split-finger flap was 2.0:1.0-2.5:1.0. During the surgery, the descending branches of lateral circumflex femoral artery and accompanying vein of flap were anastomosed end-to-end to the radial artery and vein in the recipient area, respectively, and the anterolateral femoral cutaneous nerve of flap was bridged with the superficial branch of radial nerve in the recipient area. The wounds in the donor area of flap in 14 patients were sutured directly, the wounds in the donor area of flap in 3 patients were repaired by relay superficial iliac circumflex artery perforator flap, and the wounds in the donor area of flap in 3 patients were covered by free trunk medium-thick skin graft. The survival of flap, occurrence of vascular crisis and other complications, and healing of wounds in the donor area of flap were recorded. The appearance of flap, scar hyperplasia in the donor and recipient areas and the patients' satisfaction with the shape and function of the donor and recipient areas were followed up. In 1 year after surgery, the two-point discrimination distance of the flap was measured, and the recovery of hand function was evaluated by the trial standard for the evaluation of the functions of the upper limbs of the Hand Surgery Society of the Chinese Medical Association. Results: The flaps of 17 patients survived without vascular crisis or other complications after surgery. The flap of 1 patient had poor blood circulation and partial necrosis, and the wound was healed 14 days after dressing change and grafting of split-thickness skin graft from head. Two patients had mild cyanosis at the margin of flap after surgery, which disappeared spontaneously 5 days later. Incisions at donor site, relay flaps, and skin grafts of all patients survived well. After surgery, the color and texture of flap were basically the same as that of the normal skin of hand, and linear scars were observed in the donor and recipient areas. The patients were satisfied with the recovery of appearance and function of donor and recipient areas. After 1 year of follow-up, the patients' hand sensory function recovered well, the two-point discrimination distance of flap was 4-6 mm, and the recovery of hand function was evaluated as excellent in 18 cases and good in 2 cases. Conclusions: The ultrathin anterolateral femoral flap in repairing the palmar combined with multiple finger wounds in one-stage split-finger can significantly reduce the number of surgeries and improve the function and beauty of the hand, so it is worthy of clinical promotion.

[Clinical effects of free hallux-nail flap combined with the second toe composite tissue flap in the reconstruction of damaged thumb after electrical burns].

Objective: To explore the clinical effects of free hallux-nail flap combined with the second toe composite tissue flap in the reconstruction of damaged thumb after electrical burns. Methods: A retrospective observational study was conducted. From May 2018 to April 2021, 12 male patients with thumb destructive defects caused by electrical burns who met the inclusion criteria were admitted to Zhengzhou First People's Hospital, aged 27 to 58 years, including 10 cases with degree Ⅲ thumb defect and 2 cases with degree Ⅳ thumb defect after thorough debridement. The thumb was reconstructed with free hallux-nail flap combined with composite tissue flap of the second phalangeal bone, joint, and tendon with skin island. The donor site of hallux-nail flap was covered with artificial dermis in the first stage and performed with continuous vacuum sealing drainage, and covered with medium-thickness skin graft from the groin site in the second stage. The donor site in the second toe was filled and fixed with iliac bone strips. The survival of reconstructed thumb was observed 1 week after the reconstruction surgery, the survival of skin graft in the donor site of hallux-nail flap was observed 2 weeks after skin grafting, and the callus formation of the reconstructed thumb phalanx and the second toe of the donor foot was observed by X-ray 6 weeks after the reconstruction surgery. During the follow-up, the shape of reconstructed thumb was observed and the sensory function was evaluated; the function of reconstructed thumb was evaluated with trial standard for the evaluation of the functions of the upper limbs of the Hand Surgery Society of the Chinese Medical Association; whether the interphalangeal joints of the hallux and the second toe were stiff, the scar hyperplasia of the foot donor site, and whether the walking and standing functions of the donor feet were limited were observed. Results: One week after the reconstruction surgery, all the reconstructed thumbs of the patients survived. Two weeks after skin grafting, the skin grafts in the donor site of hallux-nail flap of 11 patients survived, while the skin graft in the donor site of hallux-nail flap of 1 patient was partially necrotic, which was healed completely after 10 days' dressing change. Six weeks after the reconstruction surgery, callus formation was observed in the reconstructed thumb and the second toe of the donor foot of 10 patients, the Kirschner wires were removed; while callus formation of the reconstructed thumb was poor in 2 patients, and the Kirschner wires were removed after 2 weeks of delay. During the follow-up of 6 to 24 months, the shape of reconstructed thumb was similar to that of the healthy thumb, the discrimination distance between the two points of the reconstructed thumb was 7 to 11 mm, and the functional evaluation results were excellent in 4 cases, good in 6 cases, and fair in 2 cases. The interphalangeal joints of the hallux and the second toe of the donor foot were stiff, mild scar hyperplasia was left in the donor site of foot, and the standing and walking functions of the donor foot were not significantly limited. Conclusions: The application of free hallux-nail flap combined with the second toe composite tissue flap in the reconstruction of damaged thumb after electrical burns adopts the concept of reconstruction instead of repair to close the wound. It can restore the shape and function of the damaged thumb without causing great damage to the donor foot.

[Effects of expanded frontal-parietal pedicled flap in reconstructing cervical scar contracture deformity in children after burns].

Objective: To explore the effects of expanded frontal-parietal pedicled flap in reconstructing cervical scar contracture deformity in children after burns. Methods: A retrospective observational study was conducted. From January 2015 to December 2020, 18 male children with cervical scar contracture deformity after burns who met the inclusion criteria were admitted to Zhengzhou First People's Hospital, aged 4 to 12 years, including 10 cases with degree Ⅱ cervical scar contracture deformity and 8 cases with degree Ⅲ scar contracture deformity, and were all reconstructed with expanded frontal-parietal pedicled flap. The surgery was performed in 3 stages. In the first stage, a cylindrical skin and soft tissue expander (hereinafter referred to as expander) with rated capacity of 300 to 500 mL was placed in the frontal-parietal region. The expansion time was 4 to 6 months with the total normal saline injection volume being 2.1 to 3.0 times of the rated capacity of expander. In the second stage, expander removal, scar excision, contracture release, and flap transfer were performed, with the flap areas of 18 cm×9 cm to 23 cm×13 cm and the secondary wound areas of 16 cm×8 cm to 21 cm×11 cm after scar excision and contracture release. After 3 to 4 weeks, in the third stage, the flap pedicle was cut off and restored. The rated volume of placed expander, total normal saline injection volume, type of vascular pedicle of flap, survival of flap and reconstruction of scar after the second stage surgery were recorded. The neck range of motion and cervico-mental angle were measured before surgery and one-year after surgery. The appearance of neck, occurrence of common complications in the donor and recipient sites of children, and satisfaction of children's families for treatment effects were followed up. Data were statistically analyzed with paired sample t test. Results: All the patients successfully completed the three stages of operation. The rated volume of implanted expander was 300 mL in 6 children, 400 mL in 9 children, and 500 mL in 3 children, with the volume of normal saline injection being 630 to 1 500 mL. The type of vascular pedicle of flap was double pedicle in 13 cases and was single pedicle in 5 cases. All the flaps in 17 children survived well, and the secondary wounds after neck scar excision and contracture release were all reconstructed in one procedure. In one case, the distal blood supply of the single pedicled flap was poor after the second stage surgery, with necrosis of about 2.5 cm in length. The distal necrotic tissue was removed on 10 days after the operation, and the wound was completely closed after the flap was repositioned. In the follow-up of 6 months to 3 years post operation, the cervical scar contracture deformity in 18 children was corrected without recurrence. The flap was not bloated, the texture was soft, and the appearances of chin and neck were good. The range of motion of cervical pre-buckling, extension, left flexion, and right flexion, and cervico-mental angle in one year after operation were improved compared with those before operation (with t values of 43.10, 22.64, 27.96, 20.59, and 88.42, respectively, P<0.01). The incision in the frontal donor site was located in the hairline, the scar was slight and concealed. No complication such as cranial depression was observed in expander placement site, and the children's families were satisfied with the result of reconstruction. Conclusions: Application of expanded frontal-parietal pedicled flap in reconstructing the cervical scar contracture deformity in children after burns can obviously improve the appearance and function of neck, with unlikely recurrence of postoperative scar contractures, thus it is an ideal method of reconstruction.

Safety, pharmacokinetics, and efficacy of BPI-15086 in patients with EGFR T790M-mutated advanced non-small-cell lung cancer: results from a phase I, single-arm, multicenter study.

BACKGROUND: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) resistance frequently occurs in patients with non-small-cell lung cancer (NSCLC). EGFR Thr790Met mutation (T790M+) is seen in ∼50% of patients. We assessed the safety, tolerability, and pharmacokinetics (PK) of BPI-15086, a novel, ATP-competitive, irreversible, third-generation, mutation-selective EGFR-TKI in patients with EGFR T790M-mutated NSCLC. PATIENTS AND METHODS: This two-center, phase I, dose-escalation study included patients who were 18-65 years old, with an Eastern Cooperative Oncology Group performance status of 0-2, with histologically or cytologically confirmed locally advanced or metastatic T790M+ NSCLC who were not surgical or radiotherapy candidates, and had imaging-identified disease progression after prior EGFR-TKIs. This dose-escalation study enrolled patients using a 3 + 3 study design. Patients received 25, 50, 100, 200, and 300 mg/day orally in 21-day cycles. The primary endpoints were safety, tolerability, and PK. Secondary endpoints were objective response rate (ORR) and disease control rate (DCR). The dose-expansion study was not conducted. RESULTS: We enrolled 17 patients from 29 December 2016 to 16 May 2018, in the safety and full analysis sets. All patients completed a single dosing trial, and no adverse events (AEs) causing drug discontinuation were seen. Grade 1-2 nausea, hypoalbuminemia, and decreased appetite were the most common treatment-related AEs. Grade 3 hyperglycemia was seen in one patient dosed at 300 mg/day. The ORR and DCR were 17.7% [95% confidence interval (CI) 3.8% to 43.4%] and 47.1% (95% CI 23.0% to 72.2%), respectively. CONCLUSION: BPI-15086 is a safe and tolerable third-generation EGFR-TKI with a rationale for further clinical studies.

[Real-world study on the efficacy and prognostic predictive biomarker of patients with metastatic non-small cell lung cancer treated with programmed death-1/programmed death ligand 1 inhibitors].

Objective: To describe the actual efficacy of programmed death-1 (PD-1)/ programmed-death ligand 1 (PD-L1) inhibitors in patients with metastatic non-small cell lung cancer (NSCLC) and explore potential prognostic predictive biomarkers. Methods: Patients with metastatic NSCLC who were treated with PD-1/PD-L1 inhibitors at Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to December 2019, either as monotherapy or in combination with other agents, were consecutively enrolled into this study. We retrospectively collected the data of demographics, clinical information and pathologic assessment to evaluate the therapeutic efficacy and conduct the survival analysis. Major endpoint of our study is progression-free survival (PFS). Secondary endpoints include objective response rate (ORR), disease control rate (DCR) and overall survival (OS). Results: The ORR of 174 patients who underwent PD-1/PD-L1 inhibitor was 28.7%, and the DCR was 79.3%. Immune-related adverse events (irAEs) occurred in 23 patients (13.2%). Brain metastasis, line of treatment, and treatment patterns were associated with the ORR of metastatic NSCLC patients who underwent immunotherapy (P<0.05). After a median follow-up duration of 18.8 months, the median PFS was 10.5 months (ranged from 1.5 to 40.8 months) while the median OS was not reached. The 2-year survival rate was estimated to be 63.0%. The pathologic type was related with the PFS of metastatic NSCLC patients who underwent immunotherapy (P=0.028). Sex, age, brain metastasis and autoimmune diseases were associated with OS (P<0.05). Analysis of the receptor characteristic curve (ROC) of neutrophil/lymphocyte ratio (NLR) predicting ORR of immunotherapy in metastatic NSCLC showed that the areas under the curve of NLR before immunotherapy (NLR(C0)), NLR after one cycle of immunotherapy (NLR(C1)) and ΔNLR were 0.600, 0.706 and 0.628, respectively. Multivariate logistic regression analysis showed that NLR(C1) was an independent factor of the ORR of metastatic NSCLC patients who underwent immunotherapy (OR=0.161, 95% CI: 0.062-0.422), and the efficacy of combination therapy was better than that of single agent (OR=0.395, 95% CI: 0.174-0.896). The immunotherapy efficacy in patients without brain metastasis was better than those with metastasis (OR=0.291, 95% CI: 0.095-0.887). Multivariate Cox regression analysis showed that NLR(C1) was an independent influencing factor of PFS of metastatic NSCLC patients after immunotherapy (HR=0.480, 95% CI: 0.303-0.759). Sex (HR=0.399, 95% CI: 0.161-0.991, P=0.048), age (HR=0.356, 95% CI: 0.170-0.745, P=0.006) were independent influencing factors of OS of metastatic NSCLC patients after immunotherapy. Conclusions: PD-1/PD-L1 inhibitors are proved to be efficacious and have tolerable toxicities for patients with metastatic NSCLC. Patients at advanced age could still benefit from immunotherapy. Brain metastasis is related to compromised response. Earlier application of immunotherapy in combination with other modalities enhances the efficacy without elevating risk of irAEs. NLR(C1) is an early predictor of clinical outcome. The OS of patients younger than 75 years may be improved when treated with immunotherapy.

[A prospective randomized controlled study of the effectiveness of artificial dermis combined with split-thickness skin for repairing wounds with bone and tendon exposure in hands and feet].

Objective: To explore the clinical effects of artificial dermis combined with split-thickness skin for repairing wounds with bone and tendon exposure in hands and feet. Methods: A prospective randomized controlled study was conducted. From October 2018 to February 2020, 82 patients with bone and tendon exposed wounds in hands and feet admitted to the Department of Burns of Zhengzhou First People's Hospital who met the inclusion criteria were selected. All the patients were divided into flap group (41 cases, including 27 males and 14 females) and artificial dermis+split-thickness skin group (41 cases, including 29 males and 12 females) according to the random number table, with age of (37±7) years. After complete debridement of wounds of patients in the two groups, the wounds of patients in flap group were transplanted with anterolateral femoral free flaps; the wounds of patients in artificial dermis+split-thickness skin group were grafted with artificial dermis with continuous negative pressure suction applied, and then grafted with split-thickness skin from autologous lateral thigh once the vascularization of artificial dermis was completed. One week after autologous skin graft/flap grafting, the survival of wound graft was observed and the graft survival rate was calculated. The complete wound healing time, number of operation, length of hospital stay, hospitalization cost, and the occurrence of surgery-related complications during hospitalization after autologous skin graft/flap grafting were recorded, and the incidence of complications was calculated. Six months after autologous skin graft/flap grafting, the scar hyperplasia of recipient area was evaluated by Vancouver Scar Scale (VSS), while the recovery of hand and foot function was evaluated by Total Action Mobility (TAM) System Rating method and American Orthopaedic Foot and Ankle Society Ankle and Hindfoot Function Scale (AOFAS-AHS), respectively. Data were statistically analyzed with chi-square test, Fisher's exact probability test, and independent sample t test. Results: One week after autologous skin graft/flap grafting, the survival rates of wound grafts were similar in the two groups (P>0.05). The complete wound healing time and length of hospital stay were (29±5) and (35±5) d for patients in artificial dermis+split-thickness skin group, respectively, which were significantly longer than (22±4) and (28±5) d in flap group (t=6.96, 6.22, P<0.01). Compared with those in flap group, the number of operations was fewer (t=7.39, P<0.01), the incidence of surgery-related complications during hospitalization after autologous skin graft/flap grafting was lower (P<0.01), but there was no significant change in hospitalization cost of patients in artificial dermis+split-thickness skin group (P>0.05). Six months after autologous skin graft/flap grafting, the VSS scores of recipient area of patients in the two groups were similar (t=0.32, P>0.05); the TAM score of hand function and AOFAS-AHS score of foot function of patients in artificial dermis+split-thickness skin group were 40±6 and 62±12, respectively, which were significantly higher than 34±6 and 53±11 of flap group (t=4.66, 3.41, P<0.01). Conclusions: The combined application of artificial dermis and split-thickness skin results in fewer number of operation compared with using flaps in the repair of wounds with bone and tendon exposure in hands and feet, reducing the incidence of surgery-related complications and improving the postoperative hand and foot joint function of patients, without significant scar hyperplasia, although it may also prolong the wound healing time and length of hospital stay accordingly.

Retraction notice to "30MO ORIENT-3: A randomized, open-label, phase III study of sintilimab versus docetaxel in previously treated advanced/metastatic squamous non-small cell lung cancer (sqNSCLC)": [Annals of Oncology Volume 31, Supplement 7, December 2020, Page S1428].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article was retracted at the request of the authors. The authors of this abstract have advised that full agreement between authors and sponsors on publication of the abstract has not been reached and they are therefore unable to publish this data at present.

[Clinical effects of single pedicle transfer of expanded axial flap across the midline of the frontal-parietal region in reconstruction of large scar deformities in the face and neck].

Objective: To explore the clinical effects of single pedicle transfer of expanded axial flap across the midline of the frontal-parietal region in reconstruction of large scar deformities in the face and neck. Methods: From January 2016 to August 2019, 10 male patients, aged from 20 to 52 years with post-burn facial and cervical scar deformities, were admitted to the First People's Hospital of Zhengzhou, with the size of scar ranging from 15 cm×7 cm to 23 cm×11 cm. In the first stage, a cylindrical skin and soft tissue expander with rated capacity ranging from 400 to 600 mL was placed in the frontal-parietal region. Another cylindrical expander with rated capacity ranging from 50 to 100 mL was placed in the temporal region of the patient with scars in front of the ear and in cheek. The injection time was 3 to 5 months with the total injection volume being 1.5 to 2.5 times of the rated capacity of expander. In the second stage, the superficial temporal artery frontal branch and its branches were explored, the expander was removed, the scars in the face and neck were conducted resection and contracture relaxation, and the single pedicle transfer of expanded axial flap across the midline of the frontal-parietal region for reconstruction was performed. When the branches of the superficial temporal vessels were difficult to be detected by Doppler ultrasonic blood stream detector, the patient underwent computed tomography (CT) angiography and three-dimensional reconstruction. The donor site in frontal-parietal region was directly sutured, and the wound of the exposed donor site at the pedicle and temporal region was temporarily covered with scar skin. After the suture wound was healed and the hair in expanded flap grew out, hair removal and laser hair removal were performed. Three to four weeks after transplantation of expanded flap, the flap pedicle was cut off, restored, and trimmed in the third stage. The status about the completion of operation, the implantation of expander in the temporal region, CT angiography and three-dimensional reconstruction were recorded. The effective resection area of expanded flap, the length across the midline and the length of the pedicle, and the survival status of the expanded flap and complications after operation were observed. The appearance of donor and recipient sites, the scar recurrence, the appearance and function improvement of patients, and the satisfaction degree of patients were followed up. Results: All the 10 patients successfully completed three stages of operation, of which 6 patients had an auxiliary expander placement in the temporal region, and 5 patients underwent CT angiography and three-dimensional reconstruction. The effective resection area of expanded flap ranged from 18 cm×8 cm to 25 cm×13 cm. The distal end of the flap across the midline extended 4-6 cm to the opposite side, and the length of pedicle was 2-6 cm. All the expanded flaps of patients survived well after formation and transfer. The venous reflux disorder and obvious swelling occurred in 6 patients at the distal end of the flap after operation, and the blood supply recovered after acupuncture bloodletting, etc. Follow-up of 6 to 24 months showed that the color, texture, and thickness of the expanded flaps were similar to those of the facial skin, and no recurrence of scar was observed; the incision in the donor site of the frontal-parietal region was concealed, the hair growth of the temples and head was normal, and the reconstructed hairline was natural; compared with those before operation, the appearance, head-up, mouth-opening, and other functions of patients were significantly improved; the patients were satisfied with the effect of reconstruction. Conclusions: Clinical application of single pedicle transfer of expanded axial flap across the midline of the frontal-parietal region in reconstruction of large scar deformities in the face and neck can achieve a good appearance and function, and the donor site shows good shape, which enriches the application range of the trans-regional blood supply flap. It is a reliable method for reconstruction of large scar deformities in the face and neck.

[Clinical effect of free anterolateral thigh flap combined with arterial vascular reconstruction on repairing high-voltage electrical burn wound on the wrist].

Objective: To explore the clinical effect of free anterolateral thigh flap combined with arterial vascular reconstruction on repairing high-voltage electrical burn wound of type Ⅱ and Ⅲ on the wrist. Methods: From May 2016 to February 2019, 25 patients with deep high-voltage electrical burn wounds on the wrist were admitted to Zhengzhou First People's Hospital, including 23 males and 2 females, aged 11-63 years. Among them, 4 cases had bilateral electrical burns on the wrist, and 21 cases had unilateral electrical burns on the wrist. There were 29 wounds in 29 affected limbs with depth of full-thickness to full-thickness with tendon and bone exposure, and 17 wounds were type Ⅱ and 12 wounds were type Ⅲ. Twenty-four patients underwent CT angiography of the upper extremities before surgery, while the other one patient did not undergo the examination due to seafood allergy. There were no obvious injury to the ulnar and radial arteries in 7 affected limbs, simple ulnar artery injury in 6 affected limbs, simple radial artery injury in 7 affected limbs, and both ulnar and radial arteries injury in 9 affected limbs. The wound areas after debridement were 10 cm×7 cm-36 cm×17 cm, and the free anterolateral thigh flaps were obtained with area of 11 cm×8 cm-37 cm×18 cm for repairing the wounds. For patients with no damage of ulnar artery and radial artery, the trunk of descending branch of lateral circumflex femoral artery of the flap or combined with the thick muscle perforating branch or lateral branch was anastomosed with the ulnar or radial artery of the wound. For patients with simple ulnar artery or radial artery injury, the trunk, lateral branch, or medial branch was anastomosed with the ulnar artery or radial artery of the wound. For patients with long injury of ulnar artery and radial artery, the ulnar artery or radial artery of the wound was reconstructed with one of the above-mentioned methods, the injured artery that was not anastomosed was reconstructed with great saphenous vein, and the transplanted blood vessel was embedded in the lateral femoral muscle. The accompanying vein of the descending branch of the lateral circumflex femoral artery of the flap was anastomosed with the accompanying vein of the ulnar artery or radial artery of the wound and/or the cephalic vein. The donor sites of flaps were sutured directly or repaired with split-thickness skin graft from the thigh. The survival condition of flap and affected limb after operation and during follow-up was observed, and hand function of the affected limb during follow-up was evaluated according to the evaluation standard after repair of peripheral nerve injury in upper limbs. Results: Fifteen affected limb wounds had tissue liquefaction but healed after second debridement on 14-28 days after flap repair operation. All 29 flaps survived in the end. One patient had long ulnar artery and radial artery injuries in affected limbs and the hand was necrotic due to second embolism of the blood vessel in 1 week post operation, and the remaining affected limbs survived. During the follow-up of 6 to 30 months after operation, the flaps were slightly bloated, the affected limbs were warm with normal blood flow, and finger flexion, wrist flexion, and sensory function of hand recovered to varying degrees. The functions of the survived affected limbs were evaluated as excellent in 8 affected limbs, good in 9 affected limbs, medium in 5 affected limbs, and poor in 6 affected limbs, with an excellent and good rate of 60.71%. Conclusions: The clinical effect of free anterolateral thigh flap combined with arterial vascular reconstruction is good for repairing high-voltage electrical burn wound on the wrist, and the patency restoration of the ulnar artery and/or radial artery of the upper limb in stage Ⅰ is helpful for improving the success rate of limb salvage.

RETRACTED: ORIENT-3: A randomized, open-label, phase III study of sintilimab versus docetaxel in previously treated advanced/metastatic squamous non-small cell lung cancer (sqNSCLC).

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article was retracted at the request of the authors. The authors of this abstract have advised that full agreement between authors and sponsors on publication of the abstract has not been reached and they are therefore unable to publish this data at present.

[Effects of free anterolateral femoral or medial calf flaps in the repair of severe facial burns].

Objective: To explore the effects of free anterolateral femoral or medial calf flaps in the repair of severe facial burns. Methods: From January 2014 to October 2017, 18 patients with severe facial burns were admitted to Zhengzhou First People's Hospital, including 12 males and 6 females, aged 15-78 years. Autologous intermediate split-thickness skin grafts were transplanted to replace oral mucosa in 4 patients with perforating cheek defects, and 8 patients underwent early vacuum sealing drainage and autologous intermediate split-thickness skin grafting to reduce the wound area to 14 cm×6 cm-22 cm×14 cm before flap transplantation. The wounds of 15 patients were repaired with free anterolateral femoral flaps, and the wounds of the other 3 patients were repaired with free medial calf flaps. The area of flaps ranged from 16 cm×7 cm to 24 cm×17 cm. The facial artery or superficial temporal artery was anastomosed end-to-end with lateral femoral circumflex artery or posterior tibial artery under microscope routinely and manually, and the two accompanying veins were anastomosed end-to-end by Coupler microvascular anastomat. The donor site was sutured or transplanted with autologous intermediate split-thickness skin graft. The anastomosis time of veins was recorded. The patency rate of vascular was calculated. The survival status of flaps were observed. The recovery of recipient area was observed during follow-up. Results: The anastomosis time of two veins in this group was 6-10 minutes, with an average of 8.5 minutes. The patency rates of veins and arteries were 100%. There was no vascular crisis due to the anastomosis problem. The free flaps survived well in 16 patients; one patient had hemorrhage under the flap 6 hours after operation, and the blood circulation of flaps turned well after hemostasis by surgical exploration; the other patient had 3 cm necrosis at the distal end of flap after operation, and the wound was closed after dressing change and autologous intermediate split-thickness skin grafting. The patients were followed up for 2 to 24 months after discharge. Most of the five senses function recovered. The color and texture of the flaps were not consistent with those of the normal facial skin. Some flaps were slightly swollen. Oral integrity was restored in 4 patients with perforating cheek defect with mouth opening of 2.2-3.5 cm. Conclusions: Free anterolateral thigh flaps or medial calf flaps can repair severe facial burn wounds. It takes less time to anastomose venous vessels by microvascular anastomat during operation and can ensure the quality of venous anastomosis.

[Clinical effect of free anterolateral thigh flap in repairing large annular soft tissue defect of lower leg after burn].

Objective: To explore the clinical effect of free anterolateral thigh flap in repairing large annular soft tissue defect of lower leg after burn. Methods: From January 2014 to December 2018, 9 patients with large annular soft tissue defects of lower legs after burns were hospitalized in Zhengzhou First People's Hospital, including 1 case with wounds on both legs. After debridement, area of wounds was 16 cm×11 cm-38 cm×21 cm, and the burn wounds were repaired with free anterolateral thigh flaps in the area of 18 cm×12 cm-32 cm×24 cm. End-to-end anastomosis of posterior tibial vessels or anterior tibial vessels with lateral circumflex femoral vessels was performed in manual way or by microvascular stapler. For the affected legs without condition for anastomosis, the sound medial lower leg flaps with areas of 10 cm×8 cm-15 cm×10 cm were excised and made into skin tubes, the posterior tibial vessels of the flaps were anastomosed with the vessels of free anterolateral femoral flaps, and the wounds of the injured lower legs were repaired by bridge-type cross-over free transplantation of anterolateral thigh flaps. The pedicles were broken 4 to 5 weeks later. The donor site was transplanted with autologous intermediate split-thickness skin graft from thigh. The outcome of the treatment, the number of perforators included in the flaps, and the anastomotic vessel in the recipient area of patients were recorded. The anastomosis time between manual way and microvascular staplers was recorded and compared. The patency of blood vessels, methods of free transplantation, and follow-up condition were recorded. Data were processed with Wilcoxon rank sum test for two independent samples. Results: All the 10 free flaps and skin grafts of 9 patients survived, and all the wounds were closed by primary operation. Seven flaps contained two perforators each, and three flaps contained three perforators each. The anastomotic vessels were posterior tibial vessels in 6 recipient areas and anterior tibial vessels in 4 recipient areas. Microvascular stapler was used to anastomose 12 veins, while 8 veins and 10 arteries were anstomosed manually. The time consumed by the former method was 4.00 (3.55, 4.38) min, significantly shorter than 12.80 (12.13, 13.40) min of the latter (W=78.00, P<0.01). The patency rates of veins and arteries were 100%. There was no vascular crisis due to vascular anastomosis. Three patients underwent bridge-type cross-over free transplantation, while the others underwent conventional free transplantation. Follow-up for 3 to 30 months showed that the donor site of the thigh had good motor function, without numbness or pain, but hypertrophy of scar could be seen. Four patients had slightly overstaffed flaps transplanted in the recipient area of the lower legs, while the other patients were satisfied with their appearance, and the walking function of the affected limbs gradually recovered. Conclusions: Free anterolateral thigh flap transplantation is a safe and reliable clinical limb salvage method for the repair of large annular soft tissue defect of lower leg after burn. Intraoperative application of microvascular stapler for venous anastomosis can shorten the time of vascular anastomosis and has great clinical application value.

Data from real world to evaluate the efficacy of osimertinib in non-small cell lung cancer patients with central nervous system metastasis.

OBJECTIVES: Central nervous system (CNS) metastases are very common in patients with non-small-cell lung cancer (NSCLC). We aimed to explore the clinical impact of osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), on CNS metastases in patients with advanced NSCLC in real-world setting. METHODS: Patients with advanced NSCLC who received osimertinib after progression of early-generation EGFR-TKIs and CNS metastases on baseline brain scan were retrospectively collected. Primary outcomes were disease control rate (DCR) and progression-free survival (PFS), and secondary objectives were objective response rate (ORR), time to tumor response, median best percentage change from baseline in CNS target lesion (TL) size and safety. RESULTS: Between Apr 1, 2017, and Dec 30, 2017, 22 patients met selection criteria, 15 with ≥ 1 measurable CNS lesion (RECIST 1.1) were included in CNS evaluable for response (cEFR) set. Among the 22 patients, ORR and DCR were 40.9% and 86.4%, respectively, with median PFS of 8.5 months (95% CI 4.1, 13.0). Median intracranial PFS was not reached. Of 15 patients in cEFR set, CNS DCR was 80.0% with complete response reported in 3 patients (20.0%). Median best percentage change from baseline in CNS TL size was - 40% (range - 100 to + 60%) and median time to CNS tumor response was 1.3 months. CNS ORR was 53.3%. The safety profile was acceptable and no new unexpected findings were found. CONCLUSION: This real-world analysis further confirmed that osimertinib indeed demonstrated clinically meaningful efficacy against CNS metastases in Chinese patients with advanced NSCLC.

[The efficacy and influence factors analysis of EGFR TKIs on patients with lung adenosquamous carcinoma].

Objective: To investigate the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) on patients with lung adenosquamous carcinoma, and to analyze relative factors. Methods: From August 2007 to July 2017, 40 patients who were pathologically diagnosed as lung adenosquamous carcinoma in our hospital and received EGFR TKIs treatment were retrospectively analyzed. All patients underwent EGFR mutation detection, resulted in 11 wild type, 13 19Del, 13 21L858R mutations, and 3 uncommon EGFR mutations in 20 exon and 19/21 complex mutation. A higher frequency of EGFR mutation was found in non-smokers and patients with adenocarcinoma components over 50.0%. Results: Twenty-six (65.0%) patients had disease progression after EGFR TKIs treatment, with a median progression-free survival (PFS) of 5.5 months (95% CI 0.52-10.49 months). A total of 20 (50.0%) patients died with an median overall survival (OS) of 15 months (95% CI 11.03-18.97 months). Multivariate analysis showed that gender, age, smoking, histopathological subtypes, EGFR mutations, and brain metastasis had no influence on PFS (all P>0.05). Gender, age, smoking, histopathological subtypes, and the presence of brain metastasis during TKI treatment had no influence on OS (P>0.05), while EGFR mutation is the only influencing factor of OS (P<0.05) in the current study. Conclusions: EGFR TKIs had modest efficacy in lung adenosquamous carcinoma, especially in patients with EGFR mutation. Based on the pathological features, EGFR mutation and EGFR TKIs treatment should be introduced into the routine clinical practice to improve the survival of patients with lung adenosquamous carcinoma.

[Clinical effects of repair of wounds in fingers after electrical burn with wrist perforator free flaps].

Objective: To explore the clinical effects of repair of wounds in the fingers after electrical burn with wrist perforator free flaps. Methods: Twelve patients (13 fingers) with electrical burn were hospitalized in our burn ward from January 2016 to January 2017. After radical debridement, the size of wounds ranged from 5.0 cm×2.0 cm to 10.0 cm×7.0 cm. Wounds with size below or equal to 6.0 cm ×2.5 cm were repaired with free flaps based on the superficial palmar branch of radial artery, with flap area ranging from 2.5 cm×2.2 cm to 6.0 cm×4.5 cm. The superficial palmar branch of radial artery, subcutaneous vein, and palmar cutaneous branch of the median nerve underwent end-to-end anastomosis with digital proper artery, dorsal superficial vein, and digital proper nerve in the finger, respectively. The donor sites were sutured directly. Wounds with size larger than 6.0 cm×2.5 cm were repaired with free flaps based on the dorsal carpal branch of ulnar artery, with flap area ranging from 4.5 cm×3.0 cm to 12.0 cm×8.5 cm. The dorsal carpal branch of ulnar artery, subcutaneous vein, and medial antebrachial cutaneous nerve underwent end-to-end anastomosis with digital proper artery, dorsal superficial vein, and digital proper nerve in the finger, respectively. The donor sites were sutured directly or covered by full-thickness skin graft from abdomen. Results: Five free flaps based on the superficial palmar branch of radial artery and 8 free flaps based on the dorsal carpal branch of ulnar artery were used in the patients. In one week after surgery, 12 flaps survived completely, while one free flap based on the dorsal carpal branch of ulnar artery suffered from slight infection, after depressing change, it survived in the end. After the follow-up of half a year, the flaps were full in shape and the distance of two-point discrimination of ranged from 4.0 to 7.0 mm. The fingers showed good functional recovery and no deformity. The grade of function of the fingers was excellent in 10 cases and good in 3 cases. There were small incision scars in donor sites. Conclusions: The wrist perforator free flap is safe and reliable for repairing electrical burn wound of finger. The wounded finger shows good appearance and function after operation.

[Retrospective analysis of albumin-bound paclitaxel in the treatment of elderly patients with advanced non-small cell lung cancer].

OBJECTIVE: To observe the safety and short-term efficacy of sigle drug albumin-bound paclitaxel (ABP) in the treatment of elderly patients with advanced non-small cell lung cancer (NSCLC). METHODS: A total of 23 elderly patients with advanced NSCLC who received weekly ABP regimen (130 mg/m(2)/week) in our hospital from October 2011 to March 2014 were retrospectively evaluated. The short-term efficacy, progression-free survival (PFS), and overall survival (OS) were analyzed. RESULTS: The median treatment period was 4 cycles (2-10 cycles). Partial response, stable disease, progressive disease, overall response rate, and disease control rate were 26.1%, 43.5%, 30.4%, 26.1% and 69.6%, respectively. The median PFS was 5.33 months (95% CI: 2.95-7.70 months), while the median OS was 40.33 months (95% CI: 29.82-50.83 months). Major adverse events included leucopenia (82.6%), neutropenia (78.3%), nausea or vomiting (56.5%), fatigue (52.2%), peripheral neuropathy (26.1%), myalgia/arthralgia (30.4%), thrombocytopenia (13.0%) and arrhythmia (4.3%). The patients accompanied with chronic diseases had significantly higher incidence rate of peripheral neuropathy and myalgia/arthralgia compared with the patients without accompanied chronic diseases (50.0% vs. 9.1% and 66.7% vs. 9.1%, P<0.05 for both). CONCLUSION: The weekly single drug ABP regimen is effective and well-tolerated in elderly patients with advanced NSCLC.